O'Hara Ruth, Miller Elana, Liao Chun-Ping, Way Nate, Lin Xiaoyan, Hallmayer Joachim
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA 94305-5550, USA.
Neurosci Lett. 2006 Dec 6;409(3):205-9. doi: 10.1016/j.neulet.2006.09.047. Epub 2006 Oct 9.
A common polymorphism (Val158Met) in the gene encoding for the catechol-O-methyltransferase (COMT) enzyme has been associated with differences in prefrontal cognitive function in schizophrenic patients and healthy adults. While several studies indicate that the Met allele is associated with better performance on measures of executive function, working memory and verbal fluency, results have been inconsistent. Furthermore, fewer studies have investigated this relationship in older adults, a group known to experience impairments in prefrontal cognitive functions. Additionally, findings vary according to the gender distribution of study participants. We examined whether COMT genotype interacted with gender to impact cognition in a cohort of 163 healthy, older adults. Memory, verbal ability and areas of prefrontal cognitive function, including attention, speed-of-processing, and executive function, were assessed. We found no significant association between COMT genotype and any cognitive measure. However, gender interacted with COMT genotype to impact cognitive performance. Males homozygous for the Val allele performed better than both the Val/Met and Met/Met groups on measures of delayed recall. Heterozygous women performed better than their homozygous counterparts on the measure of verbal ability. These findings suggest that gender may be an important variable in consideration of the impact of COMT on cognition. Further, when gender is taken into consideration, any negative impact of COMT genotype may extend to cognitive domains other than those associated with prefrontal regions.
儿茶酚-O-甲基转移酶（COMT）的编码基因中一种常见的多态性（Val158Met）与精神分裂症患者及健康成年人的前额叶认知功能差异有关。虽然多项研究表明，Met等位基因与执行功能、工作记忆和言语流畅性测量中的更好表现相关，但结果并不一致。此外，较少有研究在老年人中探究这种关系，而老年人是已知前额叶认知功能受损的群体。另外，研究结果因研究参与者的性别分布而异。我们在163名健康老年人队列中研究了COMT基因型是否与性别相互作用以影响认知。评估了记忆、言语能力以及前额叶认知功能领域，包括注意力、加工速度和执行功能。我们发现COMT基因型与任何认知测量之间均无显著关联。然而，性别与COMT基因型相互作用以影响认知表现。在延迟回忆测量中，Val等位基因纯合的男性表现优于Val/Met和Met/Met组。杂合女性在言语能力测量上比纯合女性表现更好。这些发现表明，在考虑COMT对认知的影响时，性别可能是一个重要变量。此外，当考虑性别因素时，COMT基因型的任何负面影响可能会扩展到除与前额叶区域相关之外的其他认知领域。
